Longitudinal microRNA profiles in breast cancer tissue and plasma: Associations with hormone receptors, response, and survival

Table 1 Clinicopathologic characteristics of breast tumors before and after neoadjuvant chemotherapy

Characteristics		Primary tumor, n = 38	Post-NACT, n = 35	P value
Stage (AJCC)	0	0	3	0.21
	I	0	1
	IIA	5	7
	IIB	15	8
	IIIA	10	8
	IIIB	7	7
	IIIC	1	1
Category T	0	0	3	0.54
	1	2	2
	2	27	21
	3	2	2
	4	7	7
Category N	0	4	11	0.14
	1	17	11
	2	16	12
	3	1	1
Ki-67 index, median (interquartile range)		25 (15.0-38.8)	22.5 (12.9-37.85)	0.645

American Joint Committee on Cancer stage, T category, and N category are shown as frequencies (n). Ki-67 expression is reported as median with interquartile range. Comparisons between pre- and post- neoadjuvant chemotherapy groups were performed using the Cochran-Armitage test for trend and Wilcoxon rank-sum test (P value). No statistically significant differences were observed between groups. AJCC: American Joint Committee on Cancer; NACT: Neoadjuvant chemotherapy.

Table 2 Univariate and multivariate Cox regression analysis of clinicopathological factors and microRNA expression for overall survival in breast cancer patients

Variable	Univariate analysis		Multivariate analysis
	P value	Hazard ratios (95%CI)	P value	Hazard ratios (95%CI)
Age	0.370	0.9707 (0.9096-1.036)	0.01094	0.918 (0.859-0.980)
Ki-67 index	0.381	1.015 (0.9818-1.049)	0.00270	1.068 (1.023-1.116)
Subtype (HR+ vs HR-)	0.712	0.7369 (0.1456-3.729)	0.01618	0.0759 (0.0093-0.621)
miRNA-34a (high vs low)	0.218	0.4061 (0.0968-1.704)	1.23e-06	0.0165 (0.0032-0.0868)
miRNA-124a (high vs low)	0.172	0.3272 (0.0659-1.626)	0.09923	0.216 (0.035-1.336)
miRNA-137 (high vs low)	0.344	0.4595 (0.0918-2.300)	0.95869	0.956 (0.177-5.163)
miRNA-155 (high vs low)	0.367	0.5174 (0.1234-2.169)	0.96029	1.041 (0.215-5.048)
miRNA-373 (high vs low)	0.209	0.3975 (0.0944-1.675)	< 2 × 10-16	2.10e-11 (3.31e-12 to 1.34e-10)
HR+: MiRNA-373 (high vs low)	-	-	< 2 × 10-16	6.42e+10 (1.01e+10 to 4.09e+11)

Data represent the hazard ratios and 95% confidences intervals derived from Cox proportional hazards models. Univariate analysis evaluates the individual impact of each variable, while multivariate analysis adjusts for confounding factors to determine independent predictors of the outcome. Hazard ratios < 1 indicates a protective effect (decreased risk), while hazard ratios > 1 indicates an increased risk. MicroRNA (high vs low): Expression levels dichotomized based on median cutoff points. CI: Confidences interval; HR+: Hormone receptor positive; HR-: Hormone receptor negative.

Table 3 Survival proportions with 95% confidences interval at yearly time points

Time (months)	Survival proportion	95% confidences interval
0	1.000	1.000-1.000
12	0.966	0.901-1.000
24	0.880	0.759-1.000
36	0.828	0.685-1.000
48	0.776	0.618-0.975
60	0.661	0.480-0.909
72	0.601	0.415-0.870
84	0.601	0.415-0.870
96	0.601	0.415-0.870

The proportions of survival with 95% confidences intervals are presented at annual time points (12 months = 1 year). Overall survival remained above 50% throughout the study period, with an estimated survival probability of 0.601 at the end of follow-up.

Table 4 Univariate and multivariate Cox regression analysis of post- neoadjuvant chemotherapy clinicopathological factors and microRNA expression for overall survival in breast cancer patients

Variable	Univariate analysis		Multivariate analysis
	P value	Hazard ratios (95%CI)	P value	Hazard ratios (95%CI)
Age	0.530	0.980 (0.919-1.044)	0.532	0.959 (0.842-1.093)
Miller-Payne score (MPG 2, 3 vs 4, 5)	0.792	1.326 (0.162-10.840)	0.752	3.101 (0.003-3457.333)
Subtype (HR+ vs HR-)	0.897	1.113 (0.222-5.579)	0.044	0.015 (0.000-0.892)
miRNA-34a (high vs low)	0.827	1.169 (0.289-4.728)	0.600	0.485 (0.032-7.266)
miRNA-124a (high vs low)	0.642	1.394 (0.344-5.648)	0.654	1.666 (0.179-15.473)
miRNA-137 (high vs low)	0.739	0.790 (0.197-3.173)	0.284	0.188 (0.009-3.999)
miRNA-155 (high vs low)	0.974	1.023 (0.254-4.127)	0.999	3.143e-10 (0.000-Inf)
miRNA-373 (high vs low)	0.499	1.617 (0.401-6.515)	1.000	1.998 (0.000-Inf)
HR+: MiRNA-155 (high vs low)	-	-	0.999	7.324e+09 (0.000-Inf)
HR+: MiRNA-373 (high vs low)	-	-	1.000	9.290 (0.000-Inf)

Data represent the hazard ratios and 95% confidences intervals derived from Cox proportional hazards models. Univariate analysis evaluates the individual impact of each variable, while multivariate analysis adjusts for confounding factors to determine independent predictors of the outcome. Hazard ratios < 1 indicates a protective effect (decreased risk), while hazard ratios > 1 indicates an increased risk. MicroRNA (high vs low): Expression levels dichotomized based on median cutoff points. CI: Confidences interval; MPG: Miller-Payne grading; HR+: Hormone receptor positive; HR-: Hormone receptor negative.